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Background Biomarkers of exposures such as infection or environmental chemicals can be measured in small volumes of blood extracted from newborn dried blood spots (DBS) underscoring their potential utility for population-based research. However, few studies have evaluated the feasibility and utility of this resource; particularly the factors associated with parental consent, and the ability to retrieve banked samples with sufficient remaining volume for epidemiologic research. Methods At 8 months postpartum, 5,034 mothers of infants born (2008–2010) in New York (57 counties excluding New York City) were asked to consent for the use of residual DBS for the quantification of cytokines and environmental chemicals. Mothers were part of the Upstate KIDS study, a longitudinal birth cohort designed to evaluate child development through 3 years of age. Information on parental and infant characteristics was obtained from birth certificates and maternal report at 4 months postpartum. Multivariate logistic regression was used to identify factors associated with parental consent and with successful retrieval of DBS. Results Sixty-two percent ( n  = 3125) of parents consented. Factors significantly associated with consent included non-Hispanic ethnicity (odds ratio 2.04; 95 % CI: 1.43–2.94), parity (1.29; 1.05–1.57), maternal obesity (1.42; 1.11–1.80) and reported alcohol use during pregnancy (1.51; 1.12–2.06). However, these associations corresponded to small absolute differences in proportions (4 to 8 %), suggesting that the two groups remained comparable. Infant characteristics such as preterm delivery did not significantly differ by consent status among singletons and only ventilator use (OR 2.39; 95 % CI: 1.06–5.41) remained borderline significant among twins in adjusted analyses. Among consented infants, 99 % had at least one 3.2 mm punch successfully retrieved for biomarker analyses and 84 % had a full DBS circle available. Conclusion Parental characteristics varied slightly by consent, and the availability of samples for research purposes was high, demonstrating the feasibility of this resource for population based research.

Summary Objective Obesity has become a major, worldwide public health issue and is associated with a greater risk of adverse pregnancy outcomes. Leptin, a hormone produced by adipocytes, is elevated in individuals with obesity and may mediate the association between obesity and pregnancy outcomes. Though leptin levels during pregnancy have been associated with pregnancy outcomes, less is understood regarding preconception levels. Therefore, the objective of this study was to evaluate associations between preconception leptin levels and adverse pregnancy outcomes. Methods This was a prospective cohort study nested within a large randomized controlled trial conducted at four medical centres in the United States. A total of 1078 women completed the parent study; this analysis involved women who became pregnant during that study (n = 776). Patients were healthy women, ages 18 to 40, attempting to conceive, with 1 to 2 prior pregnancy losses. Participants were followed for less than or equal to 6 cycles while trying to conceive and throughout pregnancy if they conceived. Preconception leptin concentrations were measured in serum collected at baseline then categorized by tertiles (using the lowest as reference group). Weighted log‐binomial regression estimated risk ratios (RR) and 95% confidence intervals (CIs) for pregnancy loss, preterm delivery (PTD), gestational diabetes (GDM), and hypertensive disorders in pregnancy, adjusting for age, waist‐to‐hip ratio (WHR), and body mass index (BMI). Results The mean (SD) BMI in this cohort was 25.4 ± 6.0. GDM (RR 18.37; 95% CI, 2.39‐141.55) and hypertensive disorders of pregnancy (RR 2.35; 95% CI, 1.20‐4.61) risks were higher among women in the high tertile after adjusting for age and WHR. The associated risk persisted when adjusting for BMI for GDM but was attenuated for hypertensive disorders in pregnancy. Leptin levels were not associated with risk of pregnancy loss or PTD. Conclusions Women with higher baseline preconception leptin levels had a higher likelihood of experiencing some adverse pregnancy outcomes including GDM and hypertensive disorders of pregnancy. These findings warrant further evaluation, especially in light of the association between leptin and obesity.

High weight gain in pregnancy is associated with greater postpartum weight retention, yet long-term implications remain unknown. We aimed to assess whether gestational weight change was associated with mortality more than 50 years later. The Collaborative Perinatal Project (CPP) was a prospective US pregnancy cohort (1959–65). The CPP Mortality Linkage Study linked CPP participants to the National Death Index and Social Security Death Master File for vital status to 2016. Adjusted hazard ratios (HRs) with 95% CIs estimated associations between gestational weight gain and loss according to the 2009 National Academy of Medicine recommendations and mortality by pre-pregnancy BMI. The primary endpoint was all-cause mortality. Secondary endpoints included cardiovascular and diabetes underlying causes of mortality. Among 46 042 participants, 20 839 (45·3%) self-identified as Black and 21 287 (46·2%) as White. Median follow-up time was 52 years (IQR 45–54) and 17 901 (38·9%) participants died. For those who were underweight before pregnancy (BMI <18·5 kg/m2; 3809 [9·4%] of 40 689 before imputation for missing data]), weight change above recommendations was associated with increased cardiovascular mortality (HR 1·84 [95% CI 1·08–3·12]) but not all-cause mortality (1·14 [0·86–1·51]) or diabetes-related mortality (0·90 [0·13–6·35]). For those with a normal pre-pregnancy weight (BMI 18·5–24·9 kg/m2; 27 921 [68·6%]), weight change above recommendations was associated with increased all-cause (HR 1·09 [1·01–1·18]) and cardiovascular (1·20 [1·04–1·37]) mortality, but not diabetes-related mortality (0·95 [0·61–1·47]). For those who were overweight pre-pregnancy (BMI 25·0–29·9 kg/m2; 6251 [15·4%]), weight change above recommendations was associated with elevated all-cause (1·12 [1·01–1·24]) and diabetes-related (1·77 [1·23–2·54]) mortality, but not cardiovascular (1·12 [0·94–1·33]) mortality. For those with pre-pregnancy obesity (≥30·0 kg/m2; 2708 [6·7%]), all associations between gestational weight change and mortality had wide CIs and no meaningful relationships could be drawn. Weight change below recommended levels was associated only with a reduced diabetes-related mortality (0·62 [0·48–0·79]) in people with normal pre-pregnancy weight. This study's novel findings support the importance of achieving healthy gestational weight gain within recommendations, adding that the implications might extend beyond the pregnancy window to long-term health, including cardiovascular and diabetes-related mortality. National Institutes of Health.

Using a population-based birth cohort in upstate New York (2008–2010), we examined the determinants of brain-derived neurotrophic factor (BDNF) measured in newborn dried blood spots ( n = 2,637). We also examined the association between neonatal BDNF and children's development. The cohort was initially designed to examine the influence of infertility treatment on child development but found no impact. Mothers rated children's development in five domains repeatedly through age 3 years. Socioeconomic and maternal lifestyle determinants of BDNF were examined using multivariable linear regression models. Generalized linear mixed models estimated odds ratios for neonatal BDNF in relation to failing a developmental domain. Smoking and drinking in pregnancy, nulliparity, non-White ethnicity/race, and prepregnancy obesity were associated with lower neonatal BDNF. Neonatal BDNF was not associated with failure for developmental domains; however, there was an interaction between BDNF and preterm birth. In preterm infants, a higher BDNF was associated with lower odds of failing any developmental domains, after adjusting for confounders and infertility treatment. This result was particularly significant for failure in communication. Our findings suggest that BDNF levels in neonates may be impacted by maternal lifestyle characteristics. More specifically, lower neonatal BDNF might be an early marker of aberrant neurodevelopment in preterm infants.

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BACKGROUND:Prenatal exposure to persistent organic pollutants (POPs) may be associated with obesogenic effects in offspring. Our study is the first to investigate associations between concentrations of POPs from newborn dried blood spots (DBS) and birth characteristics. METHODS:Concentrations of 10 polychlorinated biphenyl congeners (PCBs), polybrominated diphenyl ether-47 (PBDE-47), and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) were measured from DBSs collected at birth from 2,065 singleton infants. DBS samples were pooled in groups of five and assayed together to reach limits of detection. Differences in risk of large for gestational age (LGA, defined as >90th percentile of birth weight for sex and gestational age), small for gestational age (SGA, <10th), and preterm birth (gestational age <37 weeks) were estimated using logistic regression per unit (ng/ml) increase in concentration of each chemical, adjusting for individual-level covariates, including maternal age, race/ethnicity, prepregnancy BMI, education, parity, smoking, and infant sex while assuming a gamma distribution and using multiple imputation to account for pools. RESULTS:There were 215 (11.3%) singletons born LGA, 158 (7.5%) born SGA, and 157 (7.6%) born preterm. Higher concentrations of POPs were positively associated with slightly higher risk of LGA and higher birth weight. CONCLUSIONS:Relationships between POPs measured in newborn DBS and birth size were mixed. Pooled analysis methods using DBS could address challenges in limits of detection and costs for population-based research.

Background/objectives Vitamin D status has been associated with fetal growth and offspring’s bone mass in some observational studies. We characterize the trajectory of total maternal serum 25-hydroxyvitamin D [25(OH)D] concentration by race and examine whether vitamin D status is associated with neonatal anthropometry and body composition as assessed by dual energy X-ray absorptiometry (DXA). Subjects/methods Three longitudinal pregnancy samples from the Memphis site of the Calcium for Preeclampsia Prevention trial (1992–1995) were used. Racial differences in total 25(OH)D trajectories ( n  = 343 women) were tested using an interaction term between blood draw gestational week and race in linear mixed-effects models. Linear regression and linear mixed-effects models estimated the adjusted associations between total 25(OH)D concentration with neonatal anthropometry and body composition ( n  = 252 with DXA) including interactions with infant sex and serum calcium. Results Total 25(OH)D concentration increased with gestational age, but its trajectory over pregnancy did not differ between African–American and Caucasian women. Deficient maternal vitamin D (25(OH)D concentration <20 ng/ml) was associated with lower neonatal total bone mineral density ( β −0.009 g/cm 2 ; 95% CI −0.016, −0.002). Among male newborns, deficiency was also associated with lower lean mass (−217 g; −391, −43) and birthweight (−308 g; −540, −76). Deficient maternal vitamin D was also associated with lower ponderal index ( β –2.3 kg/m 3 ; 95% CI −4.0, −0.5) among those in the lowest calcium tertile. Conclusion Vitamin D deficiency during pregnancy is associated with lower bone density and smaller size at birth in certain subgroups suggesting its importance in fetal development.

In this issue of Pediatric Research, Wang et al.2 explore possible links between childhood cardiovascular disease risk and subfertility in the Bogalusa Heart Study Babies sub-study. This study uniquely evaluated these associations to expand our understanding of the importance of cardiovascular health over the life course on subfertility in women. Overall, they found that childhood and adolescent risk factors in girls were generally not associated with indicators of self-reported fertility at about 45 years of age. Rather, pre-pregnancy systolic blood pressure was most consistently associated with multiple markers of infertility, such as indications of whether treatment was sought or whether a couple tried to conceive for over 12 months.

Early infant growth trajectories have been linked to obesity risk. The aim of this study was to examine early infant feeding practices in association with anthropometric measures and risk of overweight/obesity in childhood. A total of 2492 children from Upstate KIDS, a population-based longitudinal cohort, were included for the analysis. Parents reported breastfeeding and complementary food introduction from 4 to 12 months on questionnaires. Weight and height were reported at 2–3 years of age and during later follow-up at 7–9 years of age. Age and sex z-scores were calculated. Linear mixed models were conducted, adjusting for maternal and child sociodemographic factors. Approximately 54% of infants were formula-fed at <5 months of age. Compared to those formula-fed, BMI- (adjusted B, −0.23; 95% CI: −0.42, −0.05) and weight-for-age z-scores (adjusted B, −0.16; −0.28, −0.03) were lower for those exclusively breastfed. Infants breastfed for ≥12 months had a lower risk of being overweight (aRR, 0.33; 0.18, 0.59) at 2–3 years, relative to formula-fed infants. Compared to introduction at <5 months, the introduction of fruits and vegetables between 5 and 8 months was associated with lower risk of obesity at 7–9 years (aRR, 0.45; 0.22, 0.93). The type and duration of breastfeeding and delayed introduction of certain complementary foods was associated with lower childhood BMI.

Prenatal smoking exposure may lead to permanent changes in neonatal inflammation and immune response that have lifelong implications, including increased risks for atopy and respiratory disorders. The effect of maternal smoking on neonatal biomarkers of inflammation and immune response was assessed among 3459 singletons and twins in the Upstate KIDS Study. The following inflammatory biomarkers were measured using newborn dried blood spots (DBSs): interleukin (IL)-1α, IL-1 receptor antagonist, IL-6, IL-8, C-reactive protein, and tumor necrosis factor alpha. Immunoglobulins (IgE, IgA, IgM, and IgG subclasses) were also assessed. We used generalized estimating equations to calculate mean differences (β) in biomarker levels by timing of pregnancy smoking, cigarette load, and secondhand smoke exposure after adjusting for sociodemographic and lifestyle factors including maternal body mass index. Of the 344 (12%) women reporting smoking during pregnancy, about 40% continued throughout pregnancy and 13% reported smoking more than 1 pack per day. After covariate adjustment and Bonferroni correction for multiple comparisons, maternal smoking throughout pregnancy remained significantly associated with increased levels of IL-8 (β = 0.20, 95% confidence interval: 0.07, 0.32; p < .003). No significant associations were found with cigarette load or secondhand smoke exposure. Higher IgG3 levels were also associated with maternal smoking throughout pregnancy, although the association became nominally significant after adjustment for covariates (β = 0.09; 95% confidence interval: 0.0007, 0.17; p < .05). Maternal smoking throughout pregnancy was independently associated with increased IL-8 levels in newborns. Importantly, neonates of women who stopped smoking anytime in pregnancy did not have increased IL-8 levels. This study evaluated a range of inflammatory biomarkers and immunoglobulins in association with maternal smoking and timing/duration of smoking along with secondhand smoke exposure. By using DBSs, we present data from a large cohort of children born in Upstate New York. Our findings suggest that early differences in immunoregulation of neonates exposed to maternal smoking for full duration in utero may already be detected at birth.